Myocardial perfusion in cardiac amyloidosis.

AIMS: Cardiac involvement is the main driver of clinical outcomes in systemic amyloidosis and preliminary studies support the hypothesis that myocardial ischaemia contributes to cellular damage. The aims of this study were to assess the presence and mechanisms of myocardial ischaemia using cardiovascular magnetic resonance (CMR) with multiparametric mapping and histopathological assessment. METHODS AND RESULTS: Ninety-three patients with cardiac amyloidosis (CA) (light-chain amyloidosis n = 42, transthyretin amyloidosis n = 51) and 97 without CA (three-vessel coronary disease [3VD] n = 47, unobstructed coronary arteries n = 26, healthy volunteers [HV] n = 24) underwent quantitative stress perfusion CMR with myocardial blood flow (MBF) mapping. Twenty-four myocardial biopsies and three explanted hearts with CA were analysed histopathologically. Stress MBF was severely reduced in patients with CA with lower values than patients with 3VD, unobstructed coronary arteries and HV (CA: 1.04 ± 0.51 ml/min/g, 3VD: 1.35 ± 0.50 ml/min/g, unobstructed coronary arteries: 2.92 ± 0.52 ml/min/g, HV: 2.91 ± 0.73 ml/min/g; CA vs. 3VD p = 0.011, CA vs. unobstructed coronary arteries p < 0.001, CA vs. HV p < 0.001). Myocardial perfusion abnormalities correlated with amyloid burden, systolic and diastolic function, structural parameters and blood biomarkers (p < 0.05). Biopsies demonstrated abnormal vascular endothelial growth factor staining in cardiomyocytes and endothelial cells, which may be related to hypoxia conditions. Amyloid infiltration in intramural arteries was associated with severe lumen reduction and severe reduction in capillary density. CONCLUSION: Cardiac amyloidosis is associated with severe inducible myocardial ischaemia demonstrable by histology and CMR stress perfusion mapping. Histological evaluation indicates a complex pathophysiology, where in addition to systolic and diastolic dysfunction, amyloid infiltration of the epicardial arteries and disruption and rarefaction of the capillaries play a role in contributing to myocardial ischaemia.

Clinical Outcomes in Patients Receiving Originator Follitropin Alfa and Follitropin Alfa Biosimilars in Real-world Clinical Practice: A Retrospective Study.

Background: Biosimilar drugs have broadened the treatment options in assisted reproductive technology (ART). Real-world data comparing clinical outcomes of originator follitropin alfa (Gonal-f®) with its biosimilars are required to enrich the body of evidence for clinical decision-making on choice of drug. Aims: To compare the ART outcomes in patients receiving originator follitropin (Gonal-f®) and its biosimilars in clinical setting. Settings and Design: Medical records of 364 infertile women who underwent ART between 2016 and 2020 at Akanksha Hospital and Research Institute, Gujrat, India, were retrospectively analysed. Materials and Methods: Participants were divided into two cohorts based on treatment (Gonal-f® cohort; N = 174 and biosimilar cohort; N = 190), each cohort further subdivided into group A (age <35 years) and group B (age ≥35 years). Fresh or frozen embryo transfer was performed as per the standard procedures of the clinic. Pregnancy rates and live birth rate (LBR) were the primary main outcome measures in this study. Statistical Analysis Used: Descriptive statistics and Chi-square test were used for analysis. Results: The number of oocytes retrieved from Gonal-f® and biosimilar cohorts were comparable (13.3 vs. 14.4). Compared to biosimilars, Gonal-f® treatment resulted in higher yield of cleavage stage and blastocyst stage embryos, and the proportion of women with good quality embryos was higher in the Gonal-f® cohort than the biosimilar cohort (83.3% vs. 69.5%). Patients receiving Gonal-f® reported higher pregnancy rates (59.2% vs. 39.7%) and LBR (43% vs. 17.7%) compared to those receiving biosimilars. Conclusions: Gonal-f® (originator follitropin) treatment could result in higher pregnancy rates and LBR in comparison to biosimilars in real-world setting.

Midterm Outcomes in Patients With Aortic Stenosis Treated With Contemporary Balloon-Expandable and Self-Expanding Valves: Does Valve Size Have an Impact on Outcome?

Background No data currently exist comparing the contemporary iterations of balloon-expandable (BE) Edwards SAPIEN 3/Ultra and the self-expanding (SE) Medtronic Evolut PRO/R34 valves. The aim of the study was the comparison of these transcatheter heart valves with emphasis on patients with small aortic annulus. Methods and Results In this retrospective registry, periprocedural outcomes and midterm all-cause mortality were analyzed. A total of 1673 patients (917 SE versus 756 BE) were followed up for a median of 15 months. A total of 194 patients died (11.6%) during follow-up. SE and BE groups showed similar survival at 1 (92.6% versus 90.6%) and 3 (80.3% versus 85.2%) years (Plog-rank=0.136). Compared with the BE group, patients treated with the SE device had lower peak (16.3±8 mm Hg SE versus 21.9±8 mm Hg BE) and mean (8.8±5 mm Hg SE versus 11.5±5 mm Hg BE) gradients at discharge. Conversely, the BE group demonstrated lower rates of at least moderate paravalvular regurgitation postoperatively (5.6% versus 0.7% for SE and BE valves, respectively; P<0.001). In patients treated with small transcatheter heart valves (≤26 mm for SE and ≤23 mm for BE; N=284 for SE and N=260 for BE), survival was higher among patients treated with SE valves at both 1 (96.7% SE versus 92.1% BE) and 3 (91.8% SE versus 82.2% BE) years (Plog-rank=0.042). In propensity-matched patients treated with small transcatheter heart valve, there remained a trend for higher survival among the SE group at both 1 (97% SE versus 92.3% BE) and 3 years (91.8% SE versus 78.7% BE), Plog-rank=0.096). Conclusions Real-world comparison of the latest-generation SE and BE devices demonstrated similar survival up to 3 years' follow-up. In patients with small transcatheter heart valves, there may be a trend for improved survival among those treated with SE valves.

Acquired angioedema late in the course of nivolumab treatment.

INTRODUCTION: Although programmed cell death-1 inhibitors have become the mainstay of treatment for many cancers, their use can at times be accompanied by unusual side effects. CASE REPORT: We describe herein a 43-year-old patient with Lynch syndrome and colon cancer who developed facial swelling 18 months after starting nivolumab therapy. Our patient also experienced a grade 1 maculopapular rash due to this agent. Naranjo nomogram assessment showed a probable causality between nivolumab and angioedema (score of 8). MANAGEMENT & OUTCOME: Given the modest intensity of symptoms and the excellent response of metastatic colon cancer to nivolumab, this agent was continued without interruptions. She was prescribed prednisone 20 mg orally daily as needed to be taken if the swelling progressed, or if respiratory symptoms developed. The patient experienced another two similar episodes over the next months; however, they were self-limiting and did not require steroids. Subsequently, she had no further similar symptoms. DISCUSSION: Rare reports of angioedema associated with immune checkpoint inhibitor (ICI) treatment have previously been described. The exact mechanism of these phenomena is unknown, but bradykinin release leading to increased vascular permeability might be involved. Clinicians, pharmacists, and patients should be aware of this rare side effect of ICIs as it can be life-threatening when involving the respiratory tract and causing impending airway obstruction.

Prolonged Use of Tirofiban Infusion Without Percutaneous Coronary Intervention To Achieve Optimal Results in a COVID-19 Positive Patient With Inferior ST Segment Elevated Myocardial Infarction (STEMI) Secondary to Thromboembolism: A Case Report.

Severe acute respiratory syndrome­coronavirus­2 (SARS­CoV­2), responsible for COVID-19, is mainly a respiratory illness, but it can affect other organs also such as heart, kidneys, and liver. Myocardial injury from COVID-19 has been reported in hospitalized patients ranging from pericarditis and myocarditis to acute coronary syndrome (ACS). COVID-19 is highly hypercoagulable state and is associated with both central and peripheral thromboembolism. COVID 19 patients with ACS may not present with classical features of chest pain and electrocardiogram (ECG) is the most important initial investigation in these patients to assess for any ST or T waves changes. COVID-19 patients with cardiac involvement are the most vulnerable group of patients and have increased morbidity and mortality risk. COVID-19 infections can affect the cardiovascular system in patients with or without history of coronary artery disease (CAD), but the risk of type 1 or 2 myocardial infarction (MI), myocardial injury, ST segment elevation, myocarditis, heart failure, cardiogenic shock, and life threatening arrhythmias are more common in the former group. We present a case of 55-year-old patient who presented to our cardiac center with ST elevated myocardial infarction and high blood sugar level. Patient was recently diagnosed with type 2 diabetes mellitus (T2DM) but was not commenced on medications. Echocardiogram showed mildly impaired left ventricular systolic function (LVSF) with inferior wall hypokinesia, and ECG showed inferior leads ST elevation. Coronary angiogram showed severe mid-vessel lesion and occluded posterior left ventricular branch (PLV). Multiple attempts at aspirating the thrombus resulted in thrombolysis in MI grade 2 (TIMI 2) flow in the vessel and patient was commenced on a tirofiban infusion for 72 hours.

Atypical Carcinoid Syndrome in a Patient Presenting With Pericarditis and Supraventricular Tachycardia: A Case Report.

Atypical carcinoids are more uncommon than typical carcinoids, and carcinoid syndrome in general is quite rare. Mediastinal atypical carcinoid is a rare neuroendocrine tumor (NET) that spreads aggressively and rapidly. Morphologically, neuroendocrine tumors are classified into typical carcinoid, atypical carcinoid, small cell carcinoma, and large cell neuroendocrine carcinoma, and the latter two are high-grade tumors. The incidence of atypical carcinoid is rare, and the prognosis is poor, which makes larger trials difficult. It may affect the liver, lungs, or mediastinum with or without metastasis. We present a case of a 47-year-old male patient who presented with chest pain and was found to be in supraventricular tachycardia (SVT) on initial presentation to the hospital. A repeat electrocardiogram (ECG) showed widespread ST-segment elevation. A bedside echocardiogram showed a moderate pericardial effusion, and the patient underwent a coronary angiogram, which showed normal coronary arteries. A computed tomography pulmonary angiogram (CTPA) showed a right mediastinal mass, and the patient was referred to oncology following a discussion in a multidisciplinary team (MDT) meeting. He was commenced on neoadjuvant chemotherapy and has been followed up since in the outpatient clinic. This case is unique due to the initial presentation of supraventricular tachycardia and pericardial effusion.

Comparison of Doppler Flow Velocity and Thermodilution Derived Indexes of Coronary Physiology.

OBJECTIVES: The aim of this study was to compare Doppler flow velocity and thermodilution-derived indexes and to determine the optimal thermodilution-based diagnostic thresholds for coronary flow reserve (CFR). BACKGROUND: The majority of clinical data and diagnostic thresholds for flow-based indexes are derived from Doppler measurements, and correspondence with thermodilution-derived indices remain unclear. METHODS: An international multicenter registry was conducted among patients who had coronary flow measurements using both Doppler and thermodilution techniques in the same vessel and during the same procedure. RESULTS: Physiological data from 250 vessels (in 149 patients) were included in the study. A modest correlation was found between thermodilution-derived CFR (CFRthermo) and Doppler-derived CFR (CFRDoppler) (r2 = 0.36; P < 0.0001). CFRthermo overestimated CFRDoppler (mean 2.59 ± 1.46 vs 2.05 ± 0.89; P < 0.0001; mean bias 0.59 ± 1.24 by Bland-Altman analysis), the relationship being described by the equation CFRthermo = 1.04 × CFRDoppler + 0.50. The commonly used dichotomous CFRthermo threshold of 2.0 had poor sensitivity at predicting a CFRDoppler value <2.5. The optimal CFRthermo threshold was 2.5 (sensitivity 75.54%, specificity 81.25%). There was only a weak correlation between hyperemic microvascular resistance and index of microvascular resistance (r2 = 0.19; P < 0.0001), due largely to variation in the measurement of flow by each modality. Forty-four percent of patients were discordantly classified as having abnormal microvascular resistance by hyperemic microvascular resistance (≥2.5 mm Hg · cm-1 · s) and index of microvascular resistance (≥25). CONCLUSIONS: CFR calculated by thermodilution overestimates Doppler-derived CFR, while both parameters show modest correlation. The commonly used CFRthermo threshold of 2.0 has poor sensitivity for identifying vessels with diminished CFR, but using the same binary diagnostic threshold as for Doppler (<2.5) yields reasonable diagnostic accuracy. There was only a weak correlation between microvascular resistance indexes assessed by the 2 modalities.

Distinct gut and vaginal microbiota profile in women with recurrent implantation failure and unexplained infertility.

BACKGROUND: Female reproductive tract dysbiosis impacts implantation. However, whether gut dysbiosis influences implantation failure and whether it accompanies reproductive tract dysbiosis remains scantly explored. Herein, we examined the gut-vaginal microbiota axis in infertile women. METHODS: We recruited 11 fertile women as the controls, and a cohort of 20 infertile women, 10 of whom had recurrent implantation failure (RIF), and another 10 had unexplained infertility (UE). Using amplicon sequencing, which employs PCR to create sequences of DNA called amplicon, we compared the diversity, structure, and composition of faecal and vaginal bacteria of the controls with that of the infertile cohort. Of note, we could only sequence 8 vaginal samples in each group (n = 24/31). RESULT: Compared with the controls, α-diversity and ß-diversity of the gut bacteria among the infertile groups differed significantly (p < 0.05). Taxa analysis revealed enrichment of Gram-positive bacteria in the RIF group, whereas Gram-negative bacteria were relatively abundant in the UE group. Strikingly, mucus-producing genera declined in the infertile cohort (p < 0.05). Hungatella, associated with trimethylamine N-oxide (TMAO) production, were enriched in the infertile cohort (p < 0.05). Vaginal microbiota was dominated by the genus Lactobacillus, with Lactobacillus iners AB-1 being the most abundant species across the groups. Compared with the infertile cohort, overgrowth of anaerobic bacteria, associated with vaginal dysbiosis, such as Leptotrichia and Snethia, occurred in the controls. CONCLUSION: The gut microbiota had little influence on the vaginal microbiota. Gut dysbiosis and vaginal eubiosis occurred in the infertile women, whereas the opposite trend occurred in the controls.

Birth of a healthy infant after bone marrow-derived cell therapy.

Bone marrow-derived cell (BMDC) therapy has numerous applications as potential biological cells for use in regenerative medicine. Here, we present an original case of endometrial atrophy associated with genital tuberculosis in a woman who achieved a live birth with BMDC. This 27-year-old woman came to our center with endometrial atrophy and primary infertility. She had a past history of genital tuberculosis and amenorrhea. Her husband's semen quality was normal. The patient was counseled for hysteroscopy due to thin endometrium and advised in vitro fertilization (IVF) with donor eggs in lieu of poor ovarian reserve. Several attempts of IVF with hormone replacement therapy (HRT) were made, but the desired thickness of the endometrium was not achieved. Uterine artery injection of BMDC through interventional radiology was given, followed by HRT for three months, which resulted in improved endometrium. This was subsequently followed by IVF with donor egg. The treatment resulted in the conception and delivery of a 3.1-kg baby boy through lower segment caesarean section with no antenatal, intranatal or postnatal complications. Recently, there has been massive interest in stem cells as a novel treatment method for regenerative medicine, and more specifically for the regeneration of human endometrium disorders like Asherman syndrome and thin endometrium, which was the reason behind using this strategy for treatment.

Patterns of myocardial injury in recovered troponin-positive COVID-19 patients assessed by cardiovascular magnetic resonance.

BACKGROUND: Troponin elevation is common in hospitalized COVID-19 patients, but underlying aetiologies are ill-defined. We used multi-parametric cardiovascular magnetic resonance (CMR) to assess myocardial injury in recovered COVID-19 patients. METHODS AND RESULTS: One hundred and forty-eight patients (64 ± 12 years, 70% male) with severe COVID-19 infection [all requiring hospital admission, 48 (32%) requiring ventilatory support] and troponin elevation discharged from six hospitals underwent convalescent CMR (including adenosine stress perfusion if indicated) at median 68 days. Left ventricular (LV) function was normal in 89% (ejection fraction 67% ± 11%). Late gadolinium enhancement and/or ischaemia was found in 54% (80/148). This comprised myocarditis-like scar in 26% (39/148), infarction and/or ischaemia in 22% (32/148) and dual pathology in 6% (9/148). Myocarditis-like injury was limited to three or less myocardial segments in 88% (35/40) of cases with no associated LV dysfunction; of these, 30% had active myocarditis. Myocardial infarction was found in 19% (28/148) and inducible ischaemia in 26% (20/76) of those undergoing stress perfusion (including 7 with both infarction and ischaemia). Of patients with ischaemic injury pattern, 66% (27/41) had no past history of coronary disease. There was no evidence of diffuse fibrosis or oedema in the remote myocardium (T1: COVID-19 patients 1033 ± 41 ms vs. matched controls 1028 ± 35 ms; T2: COVID-19 46 ± 3 ms vs. matched controls 47 ± 3 ms). CONCLUSIONS: During convalescence after severe COVID-19 infection with troponin elevation, myocarditis-like injury can be encountered, with limited extent and minimal functional consequence. In a proportion of patients, there is evidence of possible ongoing localized inflammation. A quarter of patients had ischaemic heart disease, of which two-thirds had no previous history. Whether these observed findings represent pre-existing clinically silent disease or de novo COVID-19-related changes remain undetermined. Diffuse oedema or fibrosis was not detected.

Drug-free In vitro Activation for Primary Ovarian Insufficiency.

Primary Ovarian Insufficiency (POI) or Diminished Ovarian Reserve (DOR) are the two conditions that affects women leading to infertility due to the lack of follicular growth and ovulation. Egg / Oocyte donation remains an option for these patients. However, with the development in Reproductive medicine various novel technologies like Ovarian Cryopreservation, Fragmentation, in vitro activation with drug treatment or even drug free autotransplantation enables the possibility of activating the pool of primordial follicles that can lead to successful pregnancy outcomes. Here, we report a case of women with POI, in which drug free in vitro activation of follicles was performed, followed by autotransplantation, which resulted in successful pregnancy. This is first case report from India that shows the procedure works and can be tried for women with POI.

Quantitative cardiovascular magnetic resonance myocardial perfusion mapping to assess hyperaemic response to adenosine stress.

AIMS: Assessment of hyperaemia during adenosine stress cardiovascular magnetic resonance (CMR) remains a clinical challenge with lack of a gold-standard non-invasive clinical marker to confirm hyperaemic response. This study aimed to validate maximum stress myocardial blood flow (SMBF) measured using quantitative perfusion mapping for assessment of hyperaemic response and compare this to current clinical markers of adenosine stress. METHODS AND RESULTS: Two hundred and eighteen subjects underwent adenosine stress CMR. A derivation cohort (22 volunteers) was used to identify a SMBF threshold value for hyperaemia. This was tested in a validation cohort (37 patients with suspected coronary artery disease) who underwent invasive coronary physiology assessment on the same day as CMR. A clinical cohort (159 patients) was used to compare SMBF to other physiological markers of hyperaemia [splenic switch-off (SSO), heart rate response (HRR), and blood pressure (BP) fall]. A minimum SMBF threshold of 1.43 mL/g/min was derived from volunteer scans. All patients in the coronary physiology cohort demonstrated regional maximum SMBF (SMBFmax) >1.43 mL/g/min and invasive evidence of hyperaemia. Of the clinical cohort, 93% had hyperaemia defined by perfusion mapping compared to 71% using SSO and 81% using HRR. There was no difference in SMBFmax in those with or without SSO (2.58 ± 0.89 vs. 2.54 ± 1.04 mL/g/min, P = 0.84) but those with HRR had significantly higher SMBFmax (2.66 1.86 mL/g/min, P < 0.001). HRR >15 bpm was superior to SSO in predicting adequate increase in SMBF (AUC 0.87 vs. 0.62, P < 0.001). CONCLUSION: Adenosine-induced increase in myocardial blood flow is accurate for confirmation of hyperaemia during stress CMR studies and is superior to traditional, clinically used markers of adequate stress such as SSO and BP response.

Assessment of Multivessel Coronary Artery Disease Using Cardiovascular Magnetic Resonance Pixelwise Quantitative Perfusion Mapping.

OBJECTIVES: The authors sought to compare the diagnostic accuracy of quantitative perfusion maps to visual assessment (VA) of first-pass perfusion images for the detection of multivessel coronary artery disease (MVCAD). BACKGROUND: VA of first-pass stress perfusion cardiac magnetic resonance (CMR) may underestimate ischemia in MVCAD. Pixelwise perfusion mapping allows quantitative measurement of regional myocardial blood flow, which may improve ischemia detection in MVCAD. METHODS: One hundred fifty-one subjects recruited at 2 centers underwent stress perfusion CMR with myocardial perfusion mapping, and invasive coronary angiography with coronary physiology assessment. Ischemic burden was assessed by VA of first-pass images and by quantitative measurement of stress myocardial blood flow using perfusion maps. RESULTS: In patients with MVCAD (2-vessel [2VD] or 3-vessel disease [3VD]; n = 95), perfusion mapping identified significantly more segments with perfusion defects (median segments per patient 12 [interquartile range (IQR): 9 to 16] by mapping vs. 8 [IQR: 5 to 9.5] by VA; p < 0.001). Ischemic burden (IB) measured using mapping was higher in MVCAD compared with IB measured using VA (3VD mapping 100 % (75% to 100%) vs. first-pass 56% (38% to 81%) ; 2VD mapping 63% (50% to 75%) vs. first-pass 41% (31% to 50%); both p < 0.001), but there was no difference in single-vessel disease (mapping 25% (13% to 44%) vs. 25% (13% to 31%). Perfusion mapping was superior to VA for the correct identification of extent of coronary disease (78% vs. 58%; p < 0.001) due to better identification of 3VD (87% vs. 40%) and 2VD (71% vs. 48%). CONCLUSIONS: VA of first-pass stress perfusion underestimates ischemic burden in MVCAD. Pixelwise quantitative perfusion mapping increases the accuracy of CMR in correctly identifying extent of coronary disease. This has important implications for assessment of ischemia and therapeutic decision-making.

Bioengineered adipose-derived stem cells for targeted enzyme-prodrug therapy of ovarian cancer intraperitoneal metastasis.

The objective of this study was to develop a stem cell-based system for targeted suicide gene therapy of recurrent, metastatic, and unresectable ovarian cancer. Malignant cells were obtained from the ascites of a patient with advanced recurrent epithelial ovarian cancer (named OVASC-1). Cancer cells were characterized to determine the percentages of drug-resistant ALDH+ cells, MDR-1/ABCG2 overexpressing cells, and cancer stem-like cells. The sensitivity and resistance of the OVASC-1 cells and spheroids to the metabolites of three different enzyme/prodrug systems were assessed, and the most effective one was selected. Adipose-derived stem cells (ASCs) were genetically engineered to express recombinant secretory human carboxylesterase-2 and nanoluciferase genes for simultaneous disease therapy and quantitative imaging. Bioluminescent imaging, magnetic resonance imaging and immuno/histochemistry results show that the engineered ASCs actively targeted and localized at both tumor stroma and necrotic regions. This created the unique opportunity to deliver drugs to not only tumor supporting cells in the stroma, but also to cancer stem-like cells in necrotic/hypoxic regions. The statistical analysis of intraperitoneal OVASC-1 tumor burden and survival rates in mice shows that the administration of the bioengineered ASCs in combination with irinotecan prodrug in the designed sequence and timeline eradicated all intraperitoneal tumors and provided survival benefits. In contrast, treatment of the drug-resistant OVASC-1 tumors with cisplatin/paclitaxel (standard-of-care) did not have any statistically significant benefit. The histopathology and hematology results do not show any toxicity to major peritoneal organs. Our toxicity data in combination with efficacy outcomes delineate a nonsurgical and targeted stem cell-based approach to overcoming drug resistance in recurrent metastatic ovarian cancer.

Automated Pixel-Wise Quantitative Myocardial Perfusion Mapping by CMR to Detect Obstructive Coronary Artery Disease and Coronary Microvascular Dysfunction: Validation Against Invasive Coronary Physiology.

OBJECTIVES: This study sought to assess the performance of cardiovascular magnetic resonance (CMR) myocardial perfusion mapping against invasive coronary physiology reference standards for detecting coronary artery disease (CAD, defined by fractional flow reserve [FFR] ≤0.80), microvascular dysfunction (MVD) (defined by index of microcirculatory resistance [IMR] ≥25) and the ability to differentiate between the two. BACKGROUND: Differentiation of epicardial (CAD) and MVD in patients with stable angina remains challenging. Automated in-line CMR perfusion mapping enables quantification of myocardial blood flow (MBF) to be performed rapidly within a clinical workflow. METHODS: Fifty patients with stable angina and 15 healthy volunteers underwent adenosine stress CMR at 1.5T with quantification of MBF and myocardial perfusion reserve (MPR). FFR and IMR were measured in 101 coronary arteries during subsequent angiography. RESULTS: Twenty-seven patients had obstructive CAD and 23 had nonobstructed arteries (7 normal IMR, 16 abnormal IMR). FFR positive (epicardial stenosis) areas had significantly lower stress MBF (1.47 ± 0.48 ml/g/min) and MPR (1.75 ± 0.60) than FFR-negative IMR-positive (MVD) areas (stress MBF: 2.10 ± 0.35 ml/g/min; MPR: 2.41 ± 0.79) and normal areas (stress MBF: 2.47 ± 0.50 ml/g/min; MPR: 2.94 ± 0.81). Stress MBF ≤1.94 ml/g/min accurately detected obstructive CAD on a regional basis (area under the curve: 0.90; p < 0.001). In patients without regional perfusion defects, global stress MBF <1.82 ml/g/min accurately discriminated between obstructive 3-vessel disease and MVD (area under the curve: 0.94; p < 0.001). CONCLUSIONS: This novel automated pixel-wise perfusion mapping technique can be used to detect physiologically significant CAD defined by FFR, MVD defined by IMR, and to differentiate MVD from multivessel coronary disease. A CMR-based diagnostic algorithm using perfusion mapping for detection of epicardial disease and MVD warrants further clinical validation.

Viabahn stent graft in the management of a grade 3 coronary perforation.

BACKGROUND: Coronary artery perforation during coronary intervention has high morbidity and mortality. This case describes the collaboration between interventional cardiologists and Interventional radiologists to successfully deploy a peripheral arterial stent graft in a coronary artery that demonstrated persistent extravasation after coronary specific stent graft placement. CASE PRESENTATION: An 84 year old female patient presented with acute coronary syndrome and coronary angiography identified a right coronary artery lesion. This was dilated and stented but resulted in a grade 3 coronary perforation. Conservative treatment with balloon tamponade failed, as did placement of a covered coronary-specific stent graft. A Viabahn peripheral arterial stent graft was placed within the indwelling stents and successfully sealed the endoleak. At 6 months the patient is clinically well and follow-up imaging has demonstrated stent patency. CONCLUSIONS: In the emergency setting when coronary artery perforation fails to respond to standard initial and bail out techniques, peripheral arterial techniques and devices can be extremely useful. A good relationship between interventional cardiology and radiology is paramount.

Insight into Different Aspects of Surrogacy Practices.

Surrogacy is an important method of assisted reproductive technology wherein a woman carries pregnancy for another couple. Number of couples around the world require surrogacy services for various reasons. Although this arrangement seems to be beneficial for all parties concerned, there are complex social, ethical, moral, and legal issues associated with it. It is these complexities that have made this practice unpopular in many parts of the world. Surrogacy in India has had its own journey from India becoming popular as a surrogacy center since 2002 to the Surrogacy (Regulation) Bill, 2016, which would restrict the option of surrogacy for many. Surrogacy is an important medical service for all those couples who would otherwise not have been able to produce a child. Surrogacy would be practiced harmoniously if delicate issues associated with surrogacy will be addressed properly through appropriately framed laws which would protect the rights of surrogate mothers, intended parents, and child born through surrogacy.

A novel chemotherapeutic protocol for peritoneal metastasis and inhibition of relapse in drug resistant ovarian cancer.

The majority of ovarian cancer patients are diagnosed in late stages of the disease, in which the tumor cells have leaked into the peritoneum and are present as tumorspheres. These tumorspheres are rich in cancer stem-like cells (CSCs), which are resistant to therapy and are a major source of relapse. The purpose of this research was to identify a safe therapeutic approach that could eradicate the peritoneal CSC-rich tumorspheres and inhibit relapse. Highly metastatic ascitic cells (OVASC-1) that are resistant to standard-of-care chemotherapy due to upregulation of MDR1 gene were obtained from a patient with ovarian carcinoma and recurrent disease. CSC-rich tumorspheres were generated, characterized, and treated with different chemotherapeutics. The most effective drug combination that could eradicate tumorspheres at nanomolar levels despite upregulation of MDR1 gene was identified. Luciferase-expressing OVASC-1 cells were implanted in the peritoneum of nude mice and treated with the identified drug combination. The progression of disease, response to therapy and recurrence were studied by quantitative imaging. Toxicity to abdominal tissues was studied by histopathology. Mice implanted with intraperitoneal (IP) OVASC-1 xenografts showed limited response to combination therapy with cisplatin/paclitaxel at the maximum tolerated dose. Despite overexpression of MDR1 on OVASC-1 cells, mice treated with our combination IP low-dose MMAE and SN-38 chemotherapy showed complete response without relapse. No signs of toxicity to abdominal tissues were observed. While MMAE and SN-38 are not administered as free drugs due to their high potency and potential for systemic toxicity, our low-dose localized therapy approach effectively restricted the cytotoxic effects to the tumor cells in the peritoneum. Consequently, maximum efficacy with minimal adverse effects was achieved. These remarkable results with IP low-dose combination chemotherapy encourage investigation into its potential clinical application as either first-line therapy or in cases of acquired resistance to cisplatin and paclitaxel.

Assessing the left main stem in the cardiac catheterization laboratory. What is "significant"? Function, imaging or both?

Revascularization of significant Left Main Stem (LMS) disease improves clinical outcomes. This can be achieved through either Coronary Artery Bypass Grafting or Percutaneous coronary intervention. Defining a significant stenosis of the LMS can be challenging and debatable, as most data have been derived using angiographic assessment alone, with a threshold of 50% luminal stenosis used as a marker of functional significance. The use of adjunctive technologies like Intravascular Ultrasound and Fractional Flow Reserve has improved our ability to accurately assess the anatomical severity and physiological significance of coronary artery stenoses, much more so, than can be achieved through conventional angiography alone. An improved assessment of LMS disease through these adjunctive techniques offers procedural and clinical benefits. Rather than focus on the preferred methods of revascularisation, this article aims to highlight the common pitfalls and misconceptions in the assessment of LMS stenoses. We also propose a simple algorithm for the assessment of LMS disease to help guide revascularisation decisions.